Mandatory food fortification with folic acid – Authors' reply
Authors: Vijaya Kancherla, Lorenzo D Botto, Laura A Rowe, Nathan A Shlobin, Adrian Caceres, Anastasia Arynchyna-Smith, Kathrin Zimmerman, Jeffrey Blount, Zewdie Kibruyisfaw, Kemel A Ghotme, Santosh Karmarkar, Graham Fieggen, Sylvia Roozen, Godfrey P Oakley, Gail Rosseau, Robert J Berry
Journal: The Lancet Global Health (2022)

In their Correspondence in response to our call to action for a World Health Assembly (WHA) resolution on mandatory food fortification with folic acid,1Kancherla V Botto LD Rowe LA et al.Preventing birth defects, saving lives, and promoting health equity: an urgent call to action for universal mandatory food fortification with folic acid.Lancet Glob Health. 2022; 10: e1053-e1057Summary Full Text Full Text PDF PubMed Scopus (33) Google Scholar David Smith and colleagues express concerns about the safety of folic acid fortification, while Anita Kar and colleagues question the applicability of food fortification as a global prevention strategy for spina bifida and anencephaly. All proposed WHA resolutions should rely on strong evidence from robust human studies and ongoing experience using the proposed intervention in a variety of countries. Food fortification with folic acid, as a public health strategy, is guided by WHO.2WHOGuideline: fortification of wheat flour with vitamins and minerals as a public health strategy. World Health Organization, GenevaJune 3, 2022https://www.who.int/publications/i/item/9789240043398Date accessed: August 17, 2022Google Scholar Countries where folic acid fortification policies are in effect have documented remarkable reductions in the prevalence of spina bifida and anencephaly, and other birth defects (eg, congenital heart defects and cleft lip and palate). Once implemented, no country has ever reversed the policy. Smith and colleagues posit concerns about harm from folic acid fortification on the basis of expert opinion of old observational data, animal studies, and newly developed hypotheses. Their posited harms of folic acid do not have strong supporting evidence. They ignore recent assessments confirming the safety of folic acid fortification established over two decades of experiences in several countries, including the USA, Canada, and Latin American countries, where mandatory fortification has been successfully implemented without any attributable adverse effects.3Field MS Stover PJ Safety of folic acid.Ann N Y Acad Sci. 2018; 1414: 59-71Crossref PubMed Scopus (91) Google Scholar Their concern about metabolic syndrome in India is not supported by findings from a contemporary randomised clinical trial conducted in Nepal.4Stewart CP Christian P Schulze KJ Leclerq SC West Jr, KP Khatry SK Antenatal micronutrient supplementation reduces metabolic syndrome in 6- to 8-year-old children in rural Nepal.J Nutr. 2009; 139: 1575-1581Summary Full Text Full Text PDF PubMed Scopus (99) Google Scholar In the decades before laboratories were able to measure unmetabolised folic acid, the level of folic acid intake recommended by the US Food and Drug Administration for anaemia was many times higher than the estimated median usual folic acid intake (138 μg per day [IQR 106–176]) achieved from mandatory food fortification in the USA.5Yang Q Cogswell ME Hamner HC et al.Folic acid source, usual intake, and folate and vitamin B-12 status in US adults: National Health and Nutrition Examination Survey (NHANES) 2003-2006.Am J Clin Nutr. 2010; 91: 64-72Summary Full Text Full Text PDF PubMed Scopus (134) Google Scholar Given that there were 75 years of much higher folic acid supplementation (up to 20 000 μg per day), high levels of unmetabolised folic acid resulting from levels of folic acid added in fortification programmes seems unlikely to be a potential source of harm. Responding to Kar and colleagues, we stated in our Health Policy paper1Kancherla V Botto LD Rowe LA et al.Preventing birth defects, saving lives, and promoting health equity: an urgent call to action for universal mandatory food fortification with folic acid.Lancet Glob Health. 2022; 10: e1053-e1057Summary Full Text Full Text PDF PubMed Scopus (33) Google Scholar that multiple staple foods can be targeted for fortification, adapting to diverse dietary patterns. We referred to a synergistic approach that is context-specific, combining mandatory fortification to reach the majority of the population, while adding a more targeted supplementation programme for populations that are hard to reach or high risk.6Shlobin NA LoPresti MA Du RY Lam S Folate fortification and supplementation in prevention of folate-sensitive neural tube defects: a systematic review of policy.J Neurosurg Pediatr. 2020; 27: 294-310Crossref PubMed Scopus (11) Google Scholar We have also cited a 2018 economic evaluation7Hoddinott J The investment case for folic acid fortification in developing countries.Ann N Y Acad Sci. 2018; 1414: 72-81Crossref PubMed Scopus (33) Google Scholar in which the author found that investment in folic acid fortification in low-income and middle-income countries was favourable. We do not agree with Kar and colleagues that mandatory food fortification is a “costly” and “culturally questionable strategy”, as the evidence points differently. Kar and colleagues propose for countries to invest in a comprehensive preconception package as a better alternative to mandatory food fortification, and opine that universal food fortification is not advisable. We agree that a comprehensive preconception care package could address several potential risk factors for birth defects. However, we should not avoid or delay cost-effective and equitable mandatory food fortification in favour of preconception packages that are largely not implemented even in high-income countries. The prevalence of preconception folic acid supplement intake by women of reproductive age caps in North American and Europe at 9–78%, and is low to non-existent in Asia, the Middle East, and Africa.8Toivonen KI Lacroix E Flynn M et al.Folic acid supplementation during the preconception period: a systematic review and meta-analysis.Prev Med. 2018; 114: 1-17Crossref PubMed Scopus (51) Google Scholar Many studies surveying preconception supplement use have failed to capture the timing of folic acid use, with the unanswered question of whether women are getting this intervention as recommended.8Toivonen KI Lacroix E Flynn M et al.Folic acid supplementation during the preconception period: a systematic review and meta-analysis.Prev Med. 2018; 114: 1-17Crossref PubMed Scopus (51) Google Scholar Finally, both Smith and colleagues and Kar and colleagues recommended considering vitamin B12 for fortification. We have stated in our Health Policy paper that once a fortification policy is initiated, multiple micronutrients, including vitamin B12, can be added along with folic acid to address nutritional deficiencies at minimal cost increase to governments and food producers. Our multidisciplinary team of authors have recognised expertise on food fortification, birth defect epidemiology, the rights and needs of people with spina bifida, and clinical and neurosurgical care. Clinicians and representative organisations of people with spina bifida are advocating for mandatory folic acid fortification of food with their decades of patient care experience, appreciating the benefit of primary prevention, especially in countries where early life-saving surgical services are sparse or completely absent. We value preconception folic acid supplementation programmes, and recurrence prevention programmes for high-risk mothers who had previous pregnancies affected by spina bifida or anencephaly; however, these programmes should complement mandatory food fortification. In 2010, the 63rd WHA Resolution on Birth Defects urged member states to increase coverage of folic acid supplementation and provide equitable access to supplements. More than a decade later, we are still facing an ongoing epidemic of folic acid-preventable birth defects, and low-income and middle-income countries are seeing the highest number of affected pregnancies. A WHA resolution on folic acid fortification is required for global health equity. We declare no competing interests. Preventing birth defects, saving lives, and promoting health equity: an urgent call to action for universal mandatory food fortification with folic acidJuly 20, 2021 marked the 30th anniversary of the publication of the landmark trial by the British Medical Research Council showing unequivocally that maternal intake of folic acid (vitamin B9) starting before pregnancy prevents most cases of infant spina bifida and anencephaly—two major neural tube defects that are severe, disabling, and often fatal. Mandatory food fortification with folic acid is a safe, cost-effective, and sustainable intervention to prevent spina bifida and anencephaly. Yet few countries implement fortification with folic acid; only a quarter of all preventable spina bifida and anencephaly cases worldwide are currently avoided by food fortification. Full-Text PDF Open AccessMandatory food fortification with folic acidIn their Health Policy paper, Vijaya Kancherla and colleagues1 ask the World Health Assembly to pass a resolution for universal mandatory folic acid fortification. Such an approach would reduce the incidence of neural tube defects, but it would certainly not eliminate them because there are other causes besides low folate status, including low vitamin B12 status and maternal obesity. The authors dismiss potential harms as concerns of the past and ignore a growing evidence base of harms in the post-fortification era. Full-Text PDF Open AccessMandatory food fortification with folic acidWe would like to point out two issues of major concern in the Health Policy paper by Vijaya Kancherla and colleagues (July 2022).1 The paper calls on the World Health Assembly to ensure universal mandatory food fortification with folic acid for prevention of birth defects. The use of the term birth defects in the title is misleading, as this umbrella term includes a large spectrum of congenital disorders, few among which are folate sensitive. By linking folate-fortified foods with the term birth defects, the title erroneously suggests that folate-fortified foods can prevent all congenital anomalies. Full-Text PDF Open AccessMandatory food fortification with folic acidWe agree with Vijaya Kancherla and colleagues,1 in their Health Policy paper, that mandatory food fortification programmes promote health equity. The authors make a compelling case for the World Health Assembly to pass an urgent resolution for universal, mandatory food fortification with folic acid. We believe that this urgent need applies equally to calcium. The consequences of calcium deficiency disproportionately affect pregnant women from low-income communities,2 among whom morbidity and mortality from pre-eclampsia is one of the most striking health inequities globally. 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